Steven G. Kelsen

Emergency room assessment and treatment of patients with acute asthma: Adequacy of the conventional approach

Abstract The adequacy of emergency room treatment of patients with acute severe asthma was assessed by analyzing the course of 127 visits to the emergency room by 102 patients. Using conventional clinical criteria as an end point (i.e., disappearance of dyspnea, elimination of labored breathing and reduction or elimination of wheezing) in 85.4 per cent of these episodes the patients responded sufficiently to emergency room treatment to allow their discharge. However, the relief of airway obstruction measured directly (1 second forced expiratory volume, FEV 1 ) was modest (mean FEV 1 on discharge was 57 per cent of the predicted normal value). Approximately one-quarter of those episodes that ended in the patients discharge from the emergency room were followed by equally severe episodes within 10 days (relapse); 6 per cent of the patients initially discharged who returned to the emergency room required hospitalization. Subjects who had a relapse had significantly less improvement in FEV 1 during treatment and lower FEV 1 values at discharge than those who did not have a relapse (p 2 ] or oxygen [PaO 2 ] tension) was sufficiently reliable as an index of the degree of obstruction to substitute for the FEV 1 . We conclude that (1) the success of emergency room treatment depends on the degree of improvement in pulmonary function achieved; and (2) objective measures (e.g., FEV 1 ) of the degree of airway obstruction are helpful in predicting the outcome of emergency room treatment of patients with acute asthma.

Effects of hypercapnia and inspiratory flow-resistive loading on respiratory activity in chronic airways obstruction.

The respiratory responses to hypercapnia alone and to hypercapnia and flow-resistive loading during inspiration were studied in normal individuals and in eucapnic and hypercapnic patients with chronic airways obstruction. Responses were assessed in terms of minute ventilation and occlusion pressure (mouth pressure during airway occlusion 100 ms after the onset of inspiration). Ventilatory responses to CO2 (deltaV/deltaPCO2) were distinctly subnormal in both groups of patients with airways obstruction. The two groups of patients, however, showed different occlusion pressure responses to CO2 (deltaP100/deltaPCO2): deltaP100/deltaPCO2 was normal in the eucapnic patients but subnormal in the hypercapnic patients. Flow-resistive loading during inspiration reduced deltaV/deltaPCO2 both in normal subjects and in patients with airways obstruction. The occlusion pressure response to CO2 increased in normal subjects during flow-resistive loading but remained unchanged in both groups of patients with chronic airways obstruction. These results indicate that while chemosensitivity as determined by deltaP100/deltaPCO2 is impaired only in hypercapnic patients with chronic airways obstruction, an acute increase in flow resistance elicits a subnormal increase in respiratory efferent activity in both eucapnic and hypercapnic patients.

Airway function in sarcoidosis

Airway function was studied in 18 patients with sarcoidosis, aged 18 to 49 years. Eleven of the patients were smokers. All patients had the characteristic functional changes of restrictive lung disease: decreased lung volumes and single breath diffusing capacity, and increased static transpulmonary pressures. Abnormal airway function was demonstrated in every patient by at least one test, and nearly always by multiple tests. Specific airway conductance was abnormally low in two patients. The ratio of the 1 second forced expiratory volume to the forced vital capacity was decreased in six patients. Frequency dependence of dynamic compliance was demonstrated in eight patients. The ratio of closing volume to vital capacity was increased above age-corrected predictions in all but two patients. Upstream airway resistance was abnormally increased in 16 of the patients. These results suggest that airway dysfunction is not uncommon in sarcoidosis.

Comparison of occlusion pressure and ventilatory responses.

The airway pressure 100 msec after the onset of an inspiratory effort against a closed airway (P100, occlusion pressure) is theoretically a more accurate index of respiratory neuron motor output than ventilation. Occlusion pressure and ventilation responses to hypercapnia were compared in repeated trials in 10 normal subjects while in the seated and supine positions. During progressive hypercapnia changes in P100 were also compared to changes in tidal volume and inspiratory airflow. These studies show that occlusion pressure increases linearly with hypercapnia in both sitting and supine subjects. Changing from the seated to the supine position, or vice versa, had no significant effect on either ventilation or occlusion pressure responses to CO2. Correlations between P100 and ventilation or airflow rate were significantly higher than correlations between P100 and tidal volume or breathing frequency. Intermittent random airway occlusion had no effect on either ventilation or pattern of breathing during hypercapnia. Occlusion pressure responses were no less variable than ventilation responses in groups of subjects whether studied seated or supine. However, maintenance of a constant moderate breathing frequency (20 breaths per minute) reduced the interindividual variability in ventilation and occlusion pressure responses to hypercapnia.

Airway occlusion pressures in awake and anesthetized goats.

The pressures generated by the inspiratory muscles as they contract isometrically during airway occlusion seem to be a measure of respiratory neuron efferent activity. The ventilatory and occlusion pressure responses to increasing levels of CO2 were studied in goats, awake and anesthetized, with and without inspiratory flow resistance. Hypercapnia was produced by rebreathing. Randomly, during rebreathing, inspiratory airflow was prevented on single breaths. Ventilation and pressures developed during the first 100, 200, 300 and 400 milliseconds of an inspiratory effort against a complete occlusion increased linearly with CO2 in both awake and anesthetized animals. Anesthesia reduced both the ventilatory and occlusion pressure responses to CO2. Inspiratory resistance increased occlusion pressure responses in awake goats but not in the same animals when anesthetized. Inspiratory airflow resistance seems to augment respiratory efferent activity as reflected in the pressure responses only in conscious goats. Thus the response to an inspiratory resistance seems to depend on the state of consciousness.

Evaluation of breath holding in hypercapnia as a simple clinical test of respiratory chemosensitivity.

Breath holding was used as the basis of a simple test of respiratory chemosensitivity. Breath holding was begun at selected degrees of hypercapnia produced by CO2 rebreathing. In 16 healthy control subjects there was a linear regression of the log of breath-holding time on the PCO2 at the start of breath holding. Breath-holding time (BHT) and the slope of a log BHT/Pco2 plot were closely correlated with the ventilatory response to CO2. In five cases of the idiopathic hypoventilation syndrome, CO2 retention and reduced ventilatory response to CO2 were accompanied by prolonged breath-holding time and the regression of log BHT on Pco2 was abnormally flat. However, in 17 patients with chronic airways obstruction, breath-holding time was never prolonged and the log BHT/Pco2 relationship was normal, even though 13 had a diminished ventilatory response to CO2 and four had chronic CO2 retention. It is concluded that the BHT/Pco2 relationship provides a useful index of respiratory chemosensitivity which is not influenced by airways obstruction. This may be helpful in the detection of impaired chemosensitivity as a cause of CO2 retention even when the ventilation CO2 response is reduced non-specifically by coexisting airways obstruction.

Respiratory responses to changes in airflow resistance in conscious man

The time course and magnitude of adjustments in respiratory activity during the application and following the removal of inspiratory resistive loads were determined in conscious men. Changes in airflow resistance were made periodically during rebreathing of a gas mixture of carbon dioxide and oxygen. Ventilation, the ratio of tidal volume to inspiratory duration and the mouth pressure during airway occlusion, 100 ms after the onset of inspiration were used as measures of inspiratory neuromuscular activity. The occlusion pressure was measured during each breath using an electrically activated solenoid shutter which obstructed the airway for only the first 100 ms of each inspiration. During the second breath following the application of the resistive load, there was an increase in inspiratory output which occurred independently of changes in PCO2 and PO2. Further increases in inspiratory activity during successive loaded breaths, however, were due exclusively to changing chemical drive. The level of inspiratory neuromuscular activity remained elevated for a single breath following removal of the added resistance. Adjustments in respiratory activity were greater the more severe the load. The results suggest that non-chemically mediated respiratory compensation in conscious individuals develops rapidly and is important in maintaining ventilation when breathing is encumbered.